Efficacy and safety of metformin and sodium-glucose co-transporter-2 inhibitors in adults with type 1 diabetes: A systematic review and network meta-analysis

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AimTo compare the efficacy and safety of sodUIm-glucose co-transporter-2 (SGLT2) inhibitors and metformin in adults with type 1 diabetes mellitus (T1DM). MethodsRandomized clinical trials until February 2019, designed to assess the efficacy and safety of SGLT2 inhibitors/metformin in adults with T1DM, were searched on PubMed, EMBASE, the Cochrane Library, and Web of Science. Safety and efficacy data were synthesized using Bayesian network meta-analyses. ResultsTwenty eligible studies with 5868 participants were included in network meta-analysis. SGLT2 inhibitors provided greater reductions in HbA1c than placebo [weighted mean difference (WMD) −0.40 (95 % confidence interval (CI) −0.47, −0.32)] and metformin (WMD: −0.32; 95 % CI: −0.47, −0.14). Both SGLT2 inhibitors and metformin promoted greater reductions in body weight than placebo. SGLT2 inhibitors caused greater reductions in body weight than metformin (WMD: −1.54; 95 % CI: −2.93, −0.09). Both SGLT2 inhibitors and metformin provided greater reductions in total insulin dose than placebo, while no difference between metformin and SGLT2 inhibitors was found. No difference in severe hypoglycemia was found between SGLT2 inhibitors and metformin. SGLT2 inhibitors induced a higher risk for diabetic ketoacidosis (DKA) than metformin/placebo. ConclusionSGLT2 inhibitors provided greater reductions in HbA1c and body weight than metformin/placebo. Both SGLT2 inhibitors and metformin induced greater reductions in total insulin dosage than placebo, with no significant differences observed between SGLT2 inhibitors and metformin. SGLT2 inhibitors induced a higher risk for DKA than metformin/placebo.